ABSTRACT
Background: Previous studies have evaluated the expression of programmed cell death ligand 1 (PD-L1) in terms of genetic mutation in lung adenocarcinoma (LUAD). However, there are no corresponding large-sample studies in Chinese patients with LUAD with solid components (LUAD-SC). Furthermore, it remains unknown whether the relationship that exists between PD-L1 expression levels and clinicopathological and molecular profiles in small biopsy specimens is consistent with that in surgically-resected specimens. The present study explored the clinicopathological features and genetic correlation of PD-L1 expression in LUAD-SC. Methods: We collected 1,186 LUAD-SC specimens from Fudan University, Zhongshan Hospital. The tumors were divided into PD-L1 negative, low, and high groups according to the tumor proportion score (TPS)-assessed expression of PD-L1. The mutational information of all specimens was assessed. Each group's clinicopathological features were also assessed. The relationship between PD-L1 expression levels and clinicopathological features, the overlap with driver genes and the prognostic value were analyzed. Results: In 1,090 resected specimens, a high PD-L1 expression level was more prevalent in the group with predominant SCs, which was remarkably correlated with lymphovascular invasion and a more advanced clinical stage. In addition, the PD-L1 expression level was significantly related to EGFR, KRAS, and BRAF mutations and ROS1 fusions. Meanwhile, in 96 biopsy specimens, the solid-dominant type and EGFR showed a significant difference in PD-L1 expression. Furthermore, compared with their resected counterparts, the biopsy specimens were significantly associated with solid predominant, advanced tumor-node-metastasis (TNM) stage, and high PD-L1 expression. Finally, high PD-L1 expression can be considered a poor prognostic factor for overall survival (OS). Conclusions: LUAD-SC with high PD-L1 expression levels is linked to unique clinicopathologic characteristics as well as driver mutations. It is important to evaluate the percentage of solid components in both punctured and excised specimens, which may help identify cases of high PD-L1 expression.
ABSTRACT
BACKGROUND: Epstein-Barr virus (EBV) is well known to be associated with a lot of tumors, including lymphoma, nasopharyngeal carcinoma, EBV-associated gastric carcinoma, and some other carcinomas with similar lymphoepithelioma-like features. However, the association between EBV and thymic epithelial tumors (TETs) is inconclusive as reports in this regard are not entirely consistent and the methods employed are of different sensitivity and specificity. The geographical difference of the patients is also one of the reasons for the different points of view. METHODS: In our study, we examined 72 thymomas, including 3 cases of type A thymomas, 27 cases of type AB, 6 cases of type B1, 26 cases of type B2 and 10 cases of type B3 thymomas, and 15 thymic carcinomas to detect the viral genome at both DNA and RNA levels. The genome DNA of fresh tissues was first screened by nested polymerase chain reaction (PCR), which could be regarded as the most sensitive method to detect small amounts of DNA. Then all the tissue blocks were further submitted for viral localization by Epstein-Barr-encoded RNA (EBER) ISH. Group parameters were assessed using the chi-square test at a significance level of p < 0.05. RESULTS: Nested PCR results showed that none of type A, eight (29.6%) type AB, one (16.7%) type B1, fifteen (57.7%) type B2, and four (40.0%) type B3 were positive for EBV genome. However, none of them detected EBER expression except for one case of type B2 thymoma. Fourteen (93.3%) thymic carcinomas were positive for EBV by nested PCR, of which three displayed weak nuclear signals within the tumor cells by EBER ISH. CONCLUSIONS: These results showed that nested PCR was a sensitive method for screening the EBV genome in thymic epithelial tumors. As the malignancy of thymoma increases, the rate of EBV infection became higher. Thymic carcinomas were well associated with the Epstein-Barr virus.There was significant association between the EBV infection rate and thymoma type (p < 0.05). We further analyzed the association between EBV infection and myasthenia gravis. However, it showed no significant difference(p = 0.2754), although the EBV infection rate was higher in the thymomas with myasthenia gravis.
ABSTRACT
OBJECTIVE: Thymoma is a slow-growing epithelial tumor of thymus gland. Its size is associated with its prognosis. The aim of this study was to analyze the prognostic correlation of tumor volume and complete resection of thymoma at different Masaoka-Koga stages. METHODS: A retrospective study was carried out, using the data of 502 patients who underwent complete resection of thymectomy at Zhongshan Hospital, Fudan University, in Shanghai, China, from February 2009 to February 2016. The characteristics of the patients were collected. Using Masaoka-Koga staging system, patients were divided into four different subcohorts: Stage I, stage II, stage III and stage IVa/IVb. The relationship between tumor volume and postoperative recurrence was analyzed for each subcohort, using receiver operating curves, cutoff values were obtained. and patients were grouped according to the cutoff values. Survival analysis was performed with the help of Kaplan-Meier method, and the difference between the two survival curves was compared using log-rank test. Whether tumor volume could be used as an independent risk factor for thymoma prognosis was analyzed, using a univariate Cox proportional hazards model. RESULTS: The area under the curve was 0.718, 0.740, 0.798, and 0.804 for the stage I, II, III, and IVa/IVb subcohorts, respectively, and the cutoff values of tumor volume for predicting recurrence were 47.90 cm3, 53.70 cm3, 76.35 cm3, and 89.05 cm3, respectively. Patients with tumor volumes greater than the cutoff values had significantly shorter recurrence-free survival than those with tumor volumes less than the cutoff values (p < 0.001). The results of the univariate Cox proportional hazards model indicated that tumor volume was an independent risk factor for thymoma prognosis and for postoperative prognosis of thymoma in Masaoka-Koga stage I (p < 0.001). CONCLUSIONS: Tumor volume is significantly correlated with the postoperative prognosis of thymoma in Masaoka-Koga stage I and can serve as an independent risk factor for predicting postoperative tumor recurrence.